US6329195B1 - Cell culture apparatus - Google Patents

Cell culture apparatus Download PDF

Info

Publication number
US6329195B1
US6329195B1 US09451969 US45196999A US6329195B1 US 6329195 B1 US6329195 B1 US 6329195B1 US 09451969 US09451969 US 09451969 US 45196999 A US45196999 A US 45196999A US 6329195 B1 US6329195 B1 US 6329195B1
Authority
US
Grant status
Grant
Patent type
Prior art keywords
cell culture
gas
apparatus
cells
part
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US09451969
Inventor
Walter Pfaller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ACM-Biotech GmbH
Original Assignee
ACM-Biotech GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Grant date

Links

Images

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/04Filters; Permeable or porous membranes or plates, e.g. dialysis
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/24Gas permeable parts
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/34Internal compartments or partitions
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/44Multiple separable units; Modules
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/06Plates; Walls; Drawers; Multilayer plates
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/30Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
    • C12M41/34Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas

Abstract

A cell culture apparatus includes at least one growth support for cells which borders on at least one side to a culture medium compartment which is suppliable, preferably continuously, with liquid culture media via inflow and outflow openings. The cell culture apparatus includes at least one gas compartment which is suppliable with a defined gas or mixture of gases, wherein said gas compartment borders to the culture medium compartment via a gas permeable but liquid impermeable membrane.

Description

BACKGROUND OF THE INVENTION

Cells can be taken from tissues and grown or proliferated extracorporally. Under these conditions, some cell types develop properties which allow unlimited propagation, through permanently repeated mitoses. These cells are denoted as so-called permanent cell lines. Freshly removed cells from tissues (e.g., surgical samples, or tissues from experimental animals) most often do not display these properties. Cells of such so-called primary cultures either lack mitotic activity or perform only a few mitoses, i.e., these cells can only be cultured for a short period of time and only under loss of most of their original functional characteristics (dedifferentiation).

Adhesion of cells to their growth support and the appropriate differentiation of cells is largely dependent on the properties of the growth support (growth substrate).

The introduction of microporous growth supports made up of thin foils of either organic or inorganic materials led to an improvement in differentiation of cells in culture. This is specifically the case for those cells growing as monocellular layers (monolayers) like epithelial and endothelial cells. The culture containers used for that purpose in most cases are hollow cylinders which are sealed on one side by microporous foils on which cells are growing. These cylinders are then placed into larger culture containers in a way that culture medium can reach the cell monolayers from both the apical and the basolateral side (U.S. Pat. No. 4,608,342),the teachings of which are incorporated herein by reference. The culture medium is replaced at certain intervals. Cultures of this type are denoted as “static”. Under these conditions, compounds produced by cells can accumulate in the culture medium and exert negative effects on cell growth and differentiation. For this reason, improved conditions have been developed. Microporous growth substrates can, for example, be placed between two concentric circular mounting unites (cell carrier) and then cells seeded and attached to the growth support. Such cell carriers can then be transferred to a culture medium chamber which is separated by the carrier in two halves. Each half of the chamber can then be perfused with the same medium or media differing in composition. The cell carriers can also be stapled in a specific culture chamber and per(i)fused with culture medium (DE-PS 3923 279), the teachings of which are incorporated herein by reference. These cell culture systems are easy to handle and offer the possibility to grow and/or maintain primary cultures over longer periods of time than under static culture conditions either using solid (plastic, glass) or microporous supports. However, they have the disadvantage that only culture containers for cell carriers having a very small growth area, i.e., about 0.9 cm2, are obtainable. The per(i)fusion cell apparatus in which cell carriers can be stacked in order to obtain enough material for biochemical/cell biological analyses has the disadvantage of insufficient oxygenation of the medium between the cell carriers. Furthermore, both devices display mixing inhomogenities during continuous replacement of the growth medium by per(i)fusion.

SUMMARY OF THE INVENTION

The invention relates to a cell culture apparatus or cell culture device, respectively, with at least one growth support for cells, which borders at least on one side to a culture medium space preferably supplied with liquid medium in a continuous mode via inflow and outflow openings.

The present invention relates to a cell culture apparatus which allows the growth and maintenance of cell cultures over prolonged periods of time under conditions which closely resemble the situation within the intact organisms. According to the invention, this can be achieved by implementation of at least one gas-compartment which can be filled with a single gas or a mixture of gases and which is sealed towards the culture medium container by a membrane impermeable to liquids but permeable to gases. This allows that within the culture medium, which is in immediate contact with the cultured cells defined partial pressures (p) of oxygen (O2), carbon dioxide (CO2), nitrogen (N2), or other gases of biological or toxicological significance can be maintained. This is of specific importance, because the cell culture systems utilizing continuous replacement of culture medium available so far do not offer this possibility. None of the systems available ensures the maintenance of constant partial pressures for biologically relevant gases like oxygen or carbon dioxide. Additional advantages and details of the invention are listed below and are further illustrated by the respective figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 gives in a vertical section an example of a cell culture part of the cell culture apparatus according to the invention.

FIG. 2 gives the respective upside down view.

FIG. 3 shows in a vertical central section the gas part of the cell culture apparatus according to the invention.

FIG. 4 gives the respective upside down view, and

FIG. 5 shows in a schematic vertical section of an assembly consisting of two cell culture parts and three gas parts of the cell culture apparatus according to the invention.

DETAILED DESCRIPTION OF THE INVENTION

The cell culture apparatus model according to the invention includes a cell culture part (FIGS. 1 and 2) and a gas part (FIGS. 3 and 4) which for example can be assembled as shown in FIG. 5.

The cell culture part (ZKT) represents a ring-shaped mounting piece for a microporous growth support 1, which ensures optimum exchange of nutrients between cell culture medium and cells 2 (in this case two monolayers) thereby improving the special differentiation of cells. The administration and removal of culture media into the upper 4 a and the lower 4 b culture medium compartment of the cell culture part, ZKT, is performed via separate channels 3 for each side of the growth support. The cell culture apparatus or cell culture device, respectively, with at least one growth support for cells, which can be proximate or contiguous with culture medium space or compartment, is preferably supplied with liquid medium in a continuous mode via inflow and outflow openings. Inflow and outflow channels are designed to provide homogeneous replacement of medium and to prevent uneven mixture of medium. This design further offers the possibility to perfuse nutrients of different composition at the top (apical) and bottom (basal or basolateral, respectively) side of the growth support of the cell culture part, thereby providing organotypic culture conditions.

The cell culture part, ZKT, is separated from the gas part, GT, through a membrane 5, preferentially made of polytetrafluoroethylene, impermeable for liquid nutrients but freely permeable for gases. The gas part is designed as a separate unit of the cell culture apparatus and has the same cylindrical outer measures as the cell culture part of FIGS. 1 and 2. The gas part shown in FIG. 3 is equipped with a gas permeable membrane 5 at both sides, and is fixed with a special mounting unit 12 to achieve a gas tight seal. The gas region or gas space or gas compartment 13 is located between the two membranes 5 and connected via vertical channels 8 to a gas supply reservoir (not shown) via tubing (not shown) which allow the supply of gas in the desired concentration. The gas flows also via the vertical channels contained in the cell culture parts aligned to the top and the bottom of the gas part.

The growth support 1 for the cells to be cultured 2 are easily exchangeable so that biochemical and molecular biological parameters can easily by analyzed. The gas permeable membrane 5 can also easily be replaced. The gas part, GT (including the vertical gas channel 8), and the mounting unit 12 for the gas permeable membrane 5 are sealed against the cell culture part, ZKT, by o-rings 6. Gas parts, GT, and cell culture parts, ZKT, can be stapled as shown in FIG. 5. This allows the simultaneous cultivation of many (as many as desired) cell growth supports under conditions of continuous nutrient supply. The assembly is performed in the direction of the arrows 11. The screw-mount through aligned bores 9 (screws not shown) presses and seals all parts together. The growth area of a single growth support amounts to approximately 5 cm2.

All gas parts are connected via a channel 8 so that only one gas input connection and one gas output connection is preferred. From the channel 8 side, channels 8 a are branching off to the gas space of the gas part. The sealing between the gas channels, the gas part and the cell culture part again is performed by o-rings 6.

The two ends of the cell culture apparatus are closed with gas parts which have only one gas-permeable membrane on that side which is facing the cell culture part. The remainder is sealed tightly at position 10.

Since the distance between the membrane 5 of the gas region and the growth support of the cell culture part is small, the volume of the apical and basolateral liquid compartment (4 a and 4 b) is also small. Therefore, a quick equilibration between the gas phase in the gas part, GT, and the gases dissolved in the medium compartments of the cell culture part, ZKT, can be achieved and kept constant.

The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.

The cell culture apparatus according to the invention allows an easy change of gas partial pressures in the culture medium as well as a simple admixture of gases which may influence the function of cultivated cells (gaseous anaesthetics, nitrogen-monoxide). The partial pressures of the gases used can be measured within the gas part, GT, as well as within the cell culture part, ZKT, if necessary, using commercially available electrodes (O2, Clark-electrodes, CO2 or NO electrodes). For that purpose, appropriate o-ring sealed bores (not shown) are foreseen.

In a preferential type of the cell culture part, specifically for the cultivation of epithelial and endothelial cells or the co-cultivation of both cell types on the same growth support, electrodes for the injection of electrical current and electrodes for the continuous monitoring of potential differences brought about by the vectorial transport of charged solutes (ions) can be implemented. Current injections and registration of trans-monolayer potential differences can be performed with commercially available instrumentation. From the injected current and the resulting change in potential differences, the trans-monolayer resistance and the trans-monolayer electrical conductivity can be calculated (principle of an “Ussing” chamber). Cell culture part, ZKT, and gas part, GT, are for example made from Polysulfon and can be autoclaved according to procedures as normally provided by medical authorities. All parts of the cell culture apparatus can be used repetitively although all parts can also be manufactured as one-way articles. The o-rings used for sealing should be made from either Viton or silicone-rubber. Commercially available filter membranes can be used as microporous growth supports.

The invention is not restricted to the modes of application shown. Specifically, the form of the culture medium compartments, ZKT, and of the gas compartments, GT, as well as the respective cell culture and gas parts, can deviate from the geometry shown. In principle, the invention can also be used if only one side of the growth support covered with cells is supplied with nutrient media. The connection between cell culture part, ZKT, and gas part, GT, can be performed by any other connection material than screws, e.g., clips or similar mounting systems.

Possible applications of the cell culture apparatus according to the present invention (hereinafter referred to as Pfaller's chamber, denoted as PK) include: cultures of human, animal, plant and insect cells, as well as organs or parts thereof, derived from any species, under static as well as dynamic culturing conditions (continuous and pulsed-flow of culture media, gases and body fluids); co-cultures of different cells and/or organs or parts thereof under static as well as dynamic culturing conditions (continuous and pulsed-flow of culture media, gases and body fluids); co-cultures of different cells and/or organs or parts thereof under status as well as dynamic culturing conditions (continuous and pulsed-flow of culture media, gases and body fluids) with cell-cell contact; and co-cultures of different cells and/or organs or parts thereof under static as well as dynamic culturing conditions (continuous and pulsed-flow of culture media, gases and body fluids) without reciprocal cell contact (culturing in separated chambers, cell interactions via conditioned medium).

Further possible applications of the cell culture apparatus according to the present invention comprise the development of artificial organs and/or equivalents thereof, by use of the above-mentioned cells and/or organs or parts thereof: cultures and/or co-cultures of astrocytes, glia cells, Schwans's cells and nerve cells, in single or co-culture for investigations of the blood-brain barrier, of conduction of stimulus and of growth studies; cultures and/or co-cultures of corneal epithelial cells together with muscle cells and/or fibroblasts, melanocytes, Langerhans' cells and endothelial cells and microvascular endothelial cells as well as nerve cells; cultures and/or co-cultures of endothelial cells together with muscle cells and/or keratinocytes, fibroblasts, melanocytes, Langerhans' cells and endothelial cells and microvascular endothelial cells as well as nerve cells; cultures and/or co-cultures of keratinocytes, fibroblasts, melanocytes, Langerhans' cells, dendritic cells, endothelial cells and microvascular endothelial cells as well as nerve cells; cultures and/or co-cultures of lung epithelial cells together with keratinocytes, fibroblasts, melanocytes, dendritic cells, endothelial cells and microvascular endothelial cells as well as nerve cells; cultures and/or co-cultures of gastrointestinal epithelial cells together with lymphatic and/or muscle cells, dendritic cells, endothelial cells and microvasular endothelial cells as well as nerve cells; cultures and/or co-cultures of hepatocytes together with fibroblasts, melanocytes, dendritic cells, endothelial cells and microvascular endothelial cells, nerve cells as well as other cells present in the liver (e.g., Kupfer's star cells, etc.); cultures and/or co-cultures of kidney epithelial cells of vascular and/or tubular origin together with lymphatic and/or muscle cells, fibroblasts, dendritic cells, endothelial and microvascular endothelial cells as well as nerve cells; and cultures and/or co-cultures of lymphatic epithelial cells together with lymphatic and/or muscle cells, fibroblasts, melanocytes, dendritic cells, endothelial and microvascular endothelial cells, as well as nerve cells.

Additional applications of the cell culture apparatus according to the present invention include its application with artificial organs and/or equivalents thereof by the use of the above-mentioned cells and/or organs or parts thereof, and/or the application of the artificial organs and/or equivalents thereof which have been generated with the PK by the use of the above cells and/or organs or parts thereof, respectively: models of blood-brain barrier; neuronal models (potentials and conduction of stimuli); drug delivery; examinations of toxicity; effect of light, UV-light, microwave radiation and radiation of higher frequency; studies of cell migration; artificial organs; gas exchange; and implants.

While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims.

Claims (19)

What is claimed is:
1. A cell culture apparatus comprising at least one cell culture part having a growth support for cells which borders with two culture medium compartments which are suppliable via inflow and outflow openings by liquid culture media; and a gas part having at least one gas space which can be supplied with a gas, wherein said gas space borders the culture medium compartments via a gas permeable, liquid impermeable membrane.
2. The cell culture apparatus of claim 1 wherein said apparatus can operate in a continuous or pulse-flow mode.
3. The cell culture apparatus of claim 1 wherein said gas can include a single gas or a mixture of gases.
4. The cell culture apparatus of claim 1 wherein at least one cell culture part and at least one separate and removable gas part connected thereto, wherein said cell culture part contains at least one growth support for cells and at least one compartment for culture medium, and wherein said gas part includes said gas space and said gas permeable membrane is connected to said cell culture part.
5. The cell culture apparatus of claim 4, where a single cell culture part includes two culture medium compartments.
6. The cell culture apparatus of claim 4, wherein o-ring seals are positioned between cell culture parts and gas parts.
7. The cell culture apparatus; of claim 1 wherein said culture medium compartments are selected from a group comprising an apical compartment, a basal medium compartment, and basolateral medium compartment.
8. The cell culture apparatus of claim 1 wherein said apparatus includes cell culture parts and gas parts which can be assembled in alternating sequence to a staple, whereby the interface gas parts contain two gas permeable membranes, each bordering to the adjacent cell culture part and to gas parts, with one gas permeable membrane and one impermeable closing side.
9. The cell culture apparatus of claim 8, wherein said cell culture parts include drillings parallel to the long axis of a cylinder which allow the insertion of screws to compress the cell culture and gas parts in a tight manner or mode.
10. The cell culture apparatus of claim 9, wherein said drillings include hollow cylinders.
11. The cell culture apparatus of claim 10, wherein said hollow cylinders have the same diameter.
12. The cell culture apparatus of claim 1, wherein said liquid impermeable, gas permeable membrane includes polytetrafluoroethylene.
13. The cell culture apparatus of claim 1, wherein said cell culture part and gas parts are formed of polysulfon.
14. The cell culture apparatus of claim 1 wherein said gas space can be supplied via a removable gas line.
15. The cell culture apparatus of claim 14 wherein said removable gas line is connected to at least one gas reservoir.
16. The cell culture apparatus of claim 1, wherein said apparatus includes a system for measuring partial pressures of the gases used within the cell culture medium compartments.
17. The cell culture apparatus of claim 16, wherein said system for measuring includes an electrode.
18. A cell culture apparatus comprising:
a) growth support for cells;
b) two culture medium compartments, which are proximate to said growth support for cells, wherein said compartments include an inflow opening and an outflow opening for liquid culture media; and
c) a gas compartment, which is proximate to each said culture medium compartment, wherein said gas compartment includes a gas permeable, liquid impermeable membrane which allows passage of gas from said gas compartment to said culture medium compartments.
19. The cell culture apparatus of claim 18, wherein the apparatus includes a growth support with at least one monolayer of cells with implemented electrodes to inject electrical current and electrodes for allowing continuous measurement of potential differences across the monolayer grown on the growth support.
US09451969 1998-08-03 1999-11-30 Cell culture apparatus Expired - Fee Related US6329195B1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AT133898A AT407047B (en) 1998-08-03 1998-08-03 Cell culture device
NL1013649A NL1013649C2 (en) 1998-08-03 1999-11-23 Cell culture device.
US09451969 US6329195B1 (en) 1998-08-03 1999-11-30 Cell culture apparatus
FR9915146A FR2801899B1 (en) 1998-08-03 1999-12-01 A device for culturing cells

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
AT133898A AT407047B (en) 1998-08-03 1998-08-03 Cell culture device
DE1999213011 DE29913011U1 (en) 1998-08-03 1999-07-26 Cell culture device
NL1013649A NL1013649C2 (en) 1998-08-03 1999-11-23 Cell culture device.
US09451969 US6329195B1 (en) 1998-08-03 1999-11-30 Cell culture apparatus
FR9915146A FR2801899B1 (en) 1998-08-03 1999-12-01 A device for culturing cells

Publications (1)

Publication Number Publication Date
US6329195B1 true US6329195B1 (en) 2001-12-11

Family

ID=27421507

Family Applications (1)

Application Number Title Priority Date Filing Date
US09451969 Expired - Fee Related US6329195B1 (en) 1998-08-03 1999-11-30 Cell culture apparatus

Country Status (4)

Country Link
US (1) US6329195B1 (en)
DE (1) DE29913011U1 (en)
FR (1) FR2801899B1 (en)
NL (1) NL1013649C2 (en)

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020172621A1 (en) * 2001-05-15 2002-11-21 Emilio Barbera-Guillem Device having microchambers and microfluidics
US6548454B1 (en) * 1997-08-29 2003-04-15 Nsk Ltd. Rolling apparatus containing a liquid fluorinated polymer oil and thickening agent
US6569675B2 (en) 2000-06-16 2003-05-27 Corning Incorporated Cell cultivating flask and method for using the cell cultivating flask
US20030211458A1 (en) * 2000-05-18 2003-11-13 Merav Sunray Measurements of enzymatic activity in a single, individual cell in population
US20040029266A1 (en) * 2002-08-09 2004-02-12 Emilio Barbera-Guillem Cell and tissue culture device
US20050064524A1 (en) * 2003-08-11 2005-03-24 Mordechai Deutsch Population of cells utilizable for substance detection and methods and devices using same
US20050158846A1 (en) * 2002-04-09 2005-07-21 Hiroki Hibino Cell culture system apparatus for checking cultured cells and apparatus for culturing cells
US20050187245A1 (en) * 2004-02-03 2005-08-25 Mohammed Alnabari Stable amorphous forms of montelukast sodium
US20050221486A1 (en) * 2004-03-25 2005-10-06 Human Genome Sciences, Inc. Cell culture apparatus and methods
US20050266393A1 (en) * 2003-10-01 2005-12-01 Baxter Gregory T Circulating flow device for assays of cell cultures, cellular components and cell products
US20060003441A1 (en) * 2002-09-16 2006-01-05 Wilhelm Scherze Method for cultivating cells, particularly human or animal cells
US20060019375A1 (en) * 2002-09-16 2006-01-26 Josef Seidl Device for culturing cells, particularly human or animal cells
US20060057557A1 (en) * 2004-09-13 2006-03-16 Molecular Cytomics Ltd. Method for identifying an image of a well in an image of a well-bearing component
US20060154233A1 (en) * 2003-02-27 2006-07-13 Molecular Cytomics Ltd. Method and device for manipulating individual small objects
US20060180529A1 (en) * 2005-02-11 2006-08-17 Emilio Barbera-Guillem Bioreactor for selectively controlling the molecular diffusion between fluids
US20060223999A1 (en) * 2006-05-10 2006-10-05 Chemagis Ltd. Process for preparing montelukast and precursors thereof
US20060238548A1 (en) * 2003-07-11 2006-10-26 Stotts Jr Paul D Method and systems for controlling a computer using a video image and for combining the video image with a computer desktop
US20060275896A1 (en) * 2005-05-12 2006-12-07 James Anderson Apparatus and method for incubating cell cultures
US20070020613A1 (en) * 2001-04-25 2007-01-25 Michael Shuler Devices and methods for pharmacokinetic-based cell culture system
US20070037277A1 (en) * 2001-04-25 2007-02-15 Michael Shuler Pharmacokinetic-based culture system with biological barriers
US20070048727A1 (en) * 2001-04-25 2007-03-01 Michael Shuler Biliary barrier
US20070207537A1 (en) * 2004-09-20 2007-09-06 Zhanfeng Cui Bioreactor
US20080193596A1 (en) * 2005-07-18 2008-08-14 Suedzucker Aktiengesellschaft Mannheim/Ochsenfurt Low-Glycemic Mixtures
US20090305397A1 (en) * 2005-03-16 2009-12-10 John Robert Dodgson Cellular entity maturation and transportation systems
US20100068100A1 (en) * 2008-08-26 2010-03-18 F. Hoffmann-La Roche Ag Sample Carrier
GB2470227A (en) * 2009-05-15 2010-11-17 Kirkstall Ltd Multi-cavity bioreactor chamber
US20100316935A1 (en) * 2008-12-05 2010-12-16 Fluidic, Llc Electrochemical cells connected in fluid flow series
US7888110B2 (en) 2003-06-26 2011-02-15 Seng Enterprises Ltd. Pico liter well holding device and method of making the same
US8038964B2 (en) 2005-01-25 2011-10-18 Seng Enterprises Ltd. Device for studying individual cells
US8288120B2 (en) 2005-11-03 2012-10-16 Seng Enterprises Ltd. Method for studying floating, living cells
US8597597B2 (en) 2003-06-26 2013-12-03 Seng Enterprises Ltd. Picoliter well holding device and method of making the same
US8647861B2 (en) 2008-07-16 2014-02-11 Children's Medical Center Corporation Organ mimic device with microchannels and methods of use and manufacturing thereof
US8808541B2 (en) 2008-03-03 2014-08-19 Marwan Nasralla Dialysis cell and tray for dialysis cells
US20150191687A1 (en) * 2012-10-19 2015-07-09 Korea Reserach Institute Of Bioscience And Biotechnology Cell Culture Container Having Dual Structure, and Circulation Culture System Using Same
US9145540B1 (en) 2007-11-15 2015-09-29 Seng Enterprises Ltd. Device for the study of living cells
US9200245B2 (en) 2003-06-26 2015-12-01 Seng Enterprises Ltd. Multiwell plate
US9725687B2 (en) 2011-12-09 2017-08-08 President And Fellows Of Harvard College Integrated human organ-on-chip microphysiological systems
US9855554B2 (en) 2013-07-22 2018-01-02 President And Fellows Of Harvard College Microfluidic cartridge assembly
US9975118B2 (en) 2007-11-15 2018-05-22 Seng Enterprises Ltd. Device for the study of living cells

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10328277A1 (en) * 2003-06-23 2005-01-13 Rwth Aachen Flow chamber for in-vitro investigation of cell surface processes under microscope, comprises seal and spring clamp holding culture dish
DE102004054125B4 (en) * 2004-11-08 2011-01-05 Minucells And Minutissue Vertriebs Gmbh Gradientenkammer for culturing and / or differentiation of cells / tissues
DE102007034935B4 (en) * 2006-07-24 2014-07-17 Biocer Entwicklungs Gmbh Arrangement for online measurements on cells

Citations (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4225671A (en) * 1977-06-10 1980-09-30 Battelle-Institut E.V. Process for the in-vitro biosynthesis of hormones, especially insulin
DE3246092A1 (en) 1982-12-13 1984-06-14 Sandoz Ag Method of measuring the oxygen partial pressure in bioreactors
US4608342A (en) 1983-05-13 1986-08-26 Stephan Nees Method of growing a confluent layer of cells on a porous or semi-permeable substrate and apparatus for practicing the method
US4748124A (en) * 1984-10-30 1988-05-31 E. I. Du Pont De Nemours And Company Compartmentalized cell-culture device and method
US4762794A (en) * 1983-05-13 1988-08-09 Stephan Nees Apparatus for contacting biological cell systems with a perfusion fluid
EP0307048A2 (en) 1987-09-11 1989-03-15 Joseph Guy Cremonese Cell culture flask utilizing a membrane barrier
US4835102A (en) * 1987-03-31 1989-05-30 Eugene Bell Tissue equivalent test systems
DE3923279A1 (en) 1989-07-14 1990-01-18 Will W Prof Dr Minuth Minusheets is a new product in order to cultivate cells in any containers in highly differentiated form on a possible natural pad
US5409829A (en) 1993-09-21 1995-04-25 Becton, Dickinson And Company Device for trans-membrane co-culture of cells and a method for using same
US5459068A (en) * 1991-04-01 1995-10-17 Brigham And Women's Hospital Microassay system for assessing transmigration of PMN across epithelia in a serosal-to-mucosal direction
US5658797A (en) * 1992-03-03 1997-08-19 Bader; Augustinus Device for the treatment of cell cultures
US5688687A (en) 1995-06-07 1997-11-18 Aastrom Biosciences, Inc. Bioreactor for mammalian cell growth and maintenance
US5707869A (en) 1994-06-28 1998-01-13 Wolf; Martin L. Compartmentalized multiple well tissue culture plate
US5714384A (en) 1994-06-28 1998-02-03 Wilson; John R. Compartmentalized tissue culture bag
DE19719751A1 (en) 1997-05-10 1998-11-12 Augustinus Dr Med Bader An apparatus for culturing and / or treating cells
EP0890636A1 (en) 1997-07-11 1999-01-13 Menicon Co., Ltd. Culture vessel
US5888807A (en) * 1989-06-15 1999-03-30 The Regents Of The University Of Michigan Devices for maintaining and growing human stem and/or hematopoietics cells
US5981268A (en) 1997-05-30 1999-11-09 Board Of Trustees, Leland Stanford, Jr. University Hybrid biosensors

Patent Citations (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU727629B2
US4225671A (en) * 1977-06-10 1980-09-30 Battelle-Institut E.V. Process for the in-vitro biosynthesis of hormones, especially insulin
DE3246092A1 (en) 1982-12-13 1984-06-14 Sandoz Ag Method of measuring the oxygen partial pressure in bioreactors
US4608342A (en) 1983-05-13 1986-08-26 Stephan Nees Method of growing a confluent layer of cells on a porous or semi-permeable substrate and apparatus for practicing the method
US4762794A (en) * 1983-05-13 1988-08-09 Stephan Nees Apparatus for contacting biological cell systems with a perfusion fluid
US4748124A (en) * 1984-10-30 1988-05-31 E. I. Du Pont De Nemours And Company Compartmentalized cell-culture device and method
US4835102A (en) * 1987-03-31 1989-05-30 Eugene Bell Tissue equivalent test systems
EP0307048A2 (en) 1987-09-11 1989-03-15 Joseph Guy Cremonese Cell culture flask utilizing a membrane barrier
US5888807A (en) * 1989-06-15 1999-03-30 The Regents Of The University Of Michigan Devices for maintaining and growing human stem and/or hematopoietics cells
DE3923279A1 (en) 1989-07-14 1990-01-18 Will W Prof Dr Minuth Minusheets is a new product in order to cultivate cells in any containers in highly differentiated form on a possible natural pad
US5190878A (en) 1989-07-14 1993-03-02 Minuth Wilhelm Apparatus for cultivating cells
US5459068A (en) * 1991-04-01 1995-10-17 Brigham And Women's Hospital Microassay system for assessing transmigration of PMN across epithelia in a serosal-to-mucosal direction
US5658797A (en) * 1992-03-03 1997-08-19 Bader; Augustinus Device for the treatment of cell cultures
US5409829A (en) 1993-09-21 1995-04-25 Becton, Dickinson And Company Device for trans-membrane co-culture of cells and a method for using same
US5714384A (en) 1994-06-28 1998-02-03 Wilson; John R. Compartmentalized tissue culture bag
US5707869A (en) 1994-06-28 1998-01-13 Wolf; Martin L. Compartmentalized multiple well tissue culture plate
US5688687A (en) 1995-06-07 1997-11-18 Aastrom Biosciences, Inc. Bioreactor for mammalian cell growth and maintenance
DE19719751A1 (en) 1997-05-10 1998-11-12 Augustinus Dr Med Bader An apparatus for culturing and / or treating cells
US5981268A (en) 1997-05-30 1999-11-09 Board Of Trustees, Leland Stanford, Jr. University Hybrid biosensors
EP0890636A1 (en) 1997-07-11 1999-01-13 Menicon Co., Ltd. Culture vessel

Cited By (58)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6548454B1 (en) * 1997-08-29 2003-04-15 Nsk Ltd. Rolling apparatus containing a liquid fluorinated polymer oil and thickening agent
US20030211458A1 (en) * 2000-05-18 2003-11-13 Merav Sunray Measurements of enzymatic activity in a single, individual cell in population
US6569675B2 (en) 2000-06-16 2003-05-27 Corning Incorporated Cell cultivating flask and method for using the cell cultivating flask
US8030061B2 (en) 2001-04-25 2011-10-04 Cornell Research Foundation, Inc. Devices and methods for pharmacokinetic-based cell culture system
US20070048727A1 (en) * 2001-04-25 2007-03-01 Michael Shuler Biliary barrier
US20080166794A1 (en) * 2001-04-25 2008-07-10 Michael Shuler Devices and Methods for Pharmacokinetic-Based Cell Culture System
US20080166795A1 (en) * 2001-04-25 2008-07-10 Michael Shuler Devices and Methods for Pharmacokinetic-Based Cell Culture System
US20070020613A1 (en) * 2001-04-25 2007-01-25 Michael Shuler Devices and methods for pharmacokinetic-based cell culture system
US20070037277A1 (en) * 2001-04-25 2007-02-15 Michael Shuler Pharmacokinetic-based culture system with biological barriers
US20020172621A1 (en) * 2001-05-15 2002-11-21 Emilio Barbera-Guillem Device having microchambers and microfluidics
US6811752B2 (en) * 2001-05-15 2004-11-02 Biocrystal, Ltd. Device having microchambers and microfluidics
US7550287B2 (en) * 2002-04-09 2009-06-23 Olympus Corporation Cell culture system apparatus for checking cultured cells and apparatus for culturing cells
US20050158846A1 (en) * 2002-04-09 2005-07-21 Hiroki Hibino Cell culture system apparatus for checking cultured cells and apparatus for culturing cells
WO2004015129A3 (en) * 2002-08-09 2004-04-08 Emilio Barbera-Guillem Cell and tissue culture device
US20040029266A1 (en) * 2002-08-09 2004-02-12 Emilio Barbera-Guillem Cell and tissue culture device
WO2004015129A2 (en) * 2002-08-09 2004-02-19 Barbera-Guillem Emilio Cell and tissue culture device
US20060019375A1 (en) * 2002-09-16 2006-01-26 Josef Seidl Device for culturing cells, particularly human or animal cells
US7635575B2 (en) * 2002-09-16 2009-12-22 Pan-Biotech Gmbh Method for cultivating cells, particularly human or animal cells
US20060003441A1 (en) * 2002-09-16 2006-01-05 Wilhelm Scherze Method for cultivating cells, particularly human or animal cells
US20060154233A1 (en) * 2003-02-27 2006-07-13 Molecular Cytomics Ltd. Method and device for manipulating individual small objects
EP2394725A2 (en) 2003-02-27 2011-12-14 Seng Enterprises Limited A method and device for manipulating cells
US7405071B2 (en) 2003-02-27 2008-07-29 Seng Enterprises Ltd. Method and device for manipulating individual small objects
US8003377B2 (en) 2003-06-26 2011-08-23 Seng Enterprises Ltd. Pico liter well holding device and method of making the same
US7888110B2 (en) 2003-06-26 2011-02-15 Seng Enterprises Ltd. Pico liter well holding device and method of making the same
US9200245B2 (en) 2003-06-26 2015-12-01 Seng Enterprises Ltd. Multiwell plate
US8597597B2 (en) 2003-06-26 2013-12-03 Seng Enterprises Ltd. Picoliter well holding device and method of making the same
US20060238548A1 (en) * 2003-07-11 2006-10-26 Stotts Jr Paul D Method and systems for controlling a computer using a video image and for combining the video image with a computer desktop
US20070222796A2 (en) * 2003-07-11 2007-09-27 The University Of North Carolina At Chapel Hill Methods and systems for controlling a computer using a video image and for combining the video image with a computer desktop
US20050064524A1 (en) * 2003-08-11 2005-03-24 Mordechai Deutsch Population of cells utilizable for substance detection and methods and devices using same
US20050266393A1 (en) * 2003-10-01 2005-12-01 Baxter Gregory T Circulating flow device for assays of cell cultures, cellular components and cell products
US20050187245A1 (en) * 2004-02-03 2005-08-25 Mohammed Alnabari Stable amorphous forms of montelukast sodium
US7544805B2 (en) 2004-02-03 2009-06-09 Chemagis Ltd. Stable amorphous forms of montelukast sodium
US20050221486A1 (en) * 2004-03-25 2005-10-06 Human Genome Sciences, Inc. Cell culture apparatus and methods
US20060057557A1 (en) * 2004-09-13 2006-03-16 Molecular Cytomics Ltd. Method for identifying an image of a well in an image of a well-bearing component
US7403647B2 (en) 2004-09-13 2008-07-22 Seng Enterprises Ltd. Method for identifying an image of a well in an image of a well-bearing component
US20070207537A1 (en) * 2004-09-20 2007-09-06 Zhanfeng Cui Bioreactor
US8481325B2 (en) 2005-01-25 2013-07-09 Seng Enterprises Ltd. Device for studying individual cells
US8038964B2 (en) 2005-01-25 2011-10-18 Seng Enterprises Ltd. Device for studying individual cells
US7514256B2 (en) 2005-02-11 2009-04-07 Emilio Barbera-Guillem Bioreactor for selectively controlling the molecular diffusion between fluids
US20060180529A1 (en) * 2005-02-11 2006-08-17 Emilio Barbera-Guillem Bioreactor for selectively controlling the molecular diffusion between fluids
US20090305397A1 (en) * 2005-03-16 2009-12-10 John Robert Dodgson Cellular entity maturation and transportation systems
US7906324B2 (en) 2005-05-12 2011-03-15 The Board Of Trustees Of The University Of Alabama Apparatus and method for incubating cell cultures
US20110129915A1 (en) * 2005-05-12 2011-06-02 James Anderson Apparatus and method for incubating cell cultures
US20060275896A1 (en) * 2005-05-12 2006-12-07 James Anderson Apparatus and method for incubating cell cultures
US20080193596A1 (en) * 2005-07-18 2008-08-14 Suedzucker Aktiengesellschaft Mannheim/Ochsenfurt Low-Glycemic Mixtures
US8288120B2 (en) 2005-11-03 2012-10-16 Seng Enterprises Ltd. Method for studying floating, living cells
US20060223999A1 (en) * 2006-05-10 2006-10-05 Chemagis Ltd. Process for preparing montelukast and precursors thereof
US9739699B2 (en) 2007-11-15 2017-08-22 Seng Enterprises Ltd. Device for the study of living cells
US9145540B1 (en) 2007-11-15 2015-09-29 Seng Enterprises Ltd. Device for the study of living cells
US9975118B2 (en) 2007-11-15 2018-05-22 Seng Enterprises Ltd. Device for the study of living cells
US8808541B2 (en) 2008-03-03 2014-08-19 Marwan Nasralla Dialysis cell and tray for dialysis cells
US8647861B2 (en) 2008-07-16 2014-02-11 Children's Medical Center Corporation Organ mimic device with microchannels and methods of use and manufacturing thereof
US20100068100A1 (en) * 2008-08-26 2010-03-18 F. Hoffmann-La Roche Ag Sample Carrier
US20100316935A1 (en) * 2008-12-05 2010-12-16 Fluidic, Llc Electrochemical cells connected in fluid flow series
GB2470227A (en) * 2009-05-15 2010-11-17 Kirkstall Ltd Multi-cavity bioreactor chamber
US9725687B2 (en) 2011-12-09 2017-08-08 President And Fellows Of Harvard College Integrated human organ-on-chip microphysiological systems
US20150191687A1 (en) * 2012-10-19 2015-07-09 Korea Reserach Institute Of Bioscience And Biotechnology Cell Culture Container Having Dual Structure, and Circulation Culture System Using Same
US9855554B2 (en) 2013-07-22 2018-01-02 President And Fellows Of Harvard College Microfluidic cartridge assembly

Also Published As

Publication number Publication date Type
NL1013649C2 (en) 2001-05-28 grant
FR2801899A1 (en) 2001-06-08 application
DE29913011U1 (en) 1999-12-16 grant
FR2801899B1 (en) 2004-04-09 grant

Similar Documents

Publication Publication Date Title
US6001585A (en) Micro hollow fiber bioreactor
US5081035A (en) Bioreactor system
US3997396A (en) Method for the in vitro propagation and maintenance of cells
US5858770A (en) Cell culture plate with oxygen and carbon dioxide-permeable waterproof sealing membrane
US7033823B2 (en) Cell-cultivating device
De Bartolo et al. A novel full‐scale flat membrane bioreactor utilizing porcine hepatocytes: cell viability and tissue‐specific functions
US5602028A (en) System for growing multi-layered cell cultures
US7022518B1 (en) Apparatus and method for co-culturing of cells
US5536656A (en) Preparation of tissue equivalents by contraction of a collagen gel layered on a collagen gel
US6544788B2 (en) Disposable perfusion bioreactor for cell culture
US5763266A (en) Methods, compositions and devices for maintaining and growing human stem and/or hematopoietics cells
Kim et al. A practical guide to microfluidic perfusion culture of adherent mammalian cells
US5589112A (en) Constructing a high density cell culture system
US6844187B1 (en) Bioreactor
McLimans et al. Kinetics of gas diffusion in mammalian cell culture systems. I. Experimental
US4391912A (en) Cell cultivation method and floating animal cell culture unit for the same
US6943008B1 (en) Bioreactor for cell culture
Lowe et al. Perfluorochemicals: their applications and benefits to cell culture
US4748124A (en) Compartmentalized cell-culture device and method
US6080581A (en) Culture vessel for growing or culturing cells, cellular aggregates, tissues and organoids and methods for using same
US5801054A (en) Cell culture vessel with self-maintained atmosphere
US20020072113A1 (en) Microincubator comprising a cell culture apparatus and a transparent heater
US5989913A (en) Culture vessel for growing or culturing cells, cellular aggregates, tissues and organoids and methods for using the same
Tourovskaia et al. Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies
US5139946A (en) Dot matrix membrane cell expansion

Legal Events

Date Code Title Description
AS Assignment

Owner name: ACM-BIOTECH GMBH, GERMANY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PFALLER, WALTER;REEL/FRAME:010796/0737

Effective date: 20000412

AS Assignment

Owner name: ACM-BIOTECH GMBH, GERMANY

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ASCHENBRENNER, ANDREAS;VOGT, HANS;GORIN, JAKOB;REEL/FRAME:013000/0887;SIGNING DATES FROM 20020605 TO 20020606

REMI Maintenance fee reminder mailed
LAPS Lapse for failure to pay maintenance fees
FP Expired due to failure to pay maintenance fee

Effective date: 20051211